2015 Blog

A recent study published in the Journal of Clinical Oncology comprising a large-scale analysis of medical records revealed that men undergoing androgen deprivation (hormonal) therapy (ADT) for prostate cancer treatment may be at almost twice the risk of eventually developing Alzheimer’s disease, and that the increased likelihood of the disease is proportional to ADT duration. The researchers emphasized that their findings do not prove that ADT increases the risk of Alzheimer’s disease but clearly point to that possibility. It is thought that low levels of testosterone produced by androgen deprivation (hormonal) therapy may diminish the body’s protective effect on brain cells. There may also be evidence suggesting that the production of amyloid beta, a protein involved in Alzheimer’s pathogenesis, increases as testosterone levels diminish. The researchers are not suggesting that today’s clinical practice of treating prostate cancer with hormonal therapy be changed. However, it adds another potential undesirable side effect to those already associated with ADT such as osteoporosis, cardiac effects, loss of muscle mass and metabolic syndrome. See the entire article as published in the December 14th issue of Prostate Cancer News Weekly Digest.

Are you a man over 40 years of age and you are either concerned about or simply have some questions about prostate cancer? Hopefully you may never need treatments of any kind but being informed is positive. The November, 2014 Prostate Cancer Research Institute (PCRI) Insights contains a collection of blogs and videos discussing the topics of prostate screening, prostate magnetic resonance imaging (MRI), newly diagnosed cancers, their active surveillance and cancer recurrence.

The screening portion (see link) discusses the prostate-specific antigen (PSA) test and risks and benefits of screening including a video. This section also includes information on prostate imaging, 12-core needle prostate biopsies, pathology results as defined by Gleason scores, use of MRI prostate scanning using 3 Tesla (3T) MRI instruments and multi-parametric targeted biopsies (if needed). A listing of 3T imaging centers is also included.

A second section includes a video discussing PSA values, more information on prostate biopsies, their benefits and side effects, pathology results as defined by Gleason Scores, 3T MRI imaging and targeted biopsies, and a blood test called the 4K test which may be useful in determining aggressive cancers if present.

A recent study from UCLA published in the December 1st issue of Cancer, included 3,600 men who had opted for active surveillance in place of aggressive treatment as a means of following the status of their prostate cancer. The study found that only 4.5% received proper monitoring in collaboration with their physician. Recommended monitoring includes regular prostate-specific antigen (PSA) screening, physical exams and at least one prostate biopsy every two years. The study urges that before a patient and his physician decide on a prostate cancer strategy of active surveillance, they should mutually commit to closely monitoring the cancer via such PSA testing, physical exams and repeat biopsies as necessary. A summary of the study was published in MedLine Plus from the National Institutes of Health (NIH). For further details, see the following article published online in Prostate Cancer News Today on December 2nd. A excellent summary of these developments was also published in Cancer Network of the journal Oncology, December 3, 2015.

The following is an edited version of a November 30th blog from Prostate Snatchers. While I have experienced stressful episodes in my 20-year cancer experience, I find nothing works better than entrusting my body and its imperfections to its Creator with whom we can have a personal relationship through Jesus Christ.

Whether you are newly diagnosed with prostate cancer, or coping with bone metastases, learning about chronic stress and its negative impact on your body is almost as critical to your healing as whatever treatment you choose.

Short-term stress, a single episode of acute stress, generally doesn’t cause problems. However, chronic emotional stress, caused by situations or events that last over a period of time, takes a significant toll on the body. Furthermore, this kind of prolonged stress suppresses the immune system, profoundly affecting its ability to detect defective or cancerous cells and destroy them.

Persistent feelings of fear, anxiety and unrelieved stress trigger the fight-or-flight response system that our ancestors relied upon. When a threat is recognized, heart rate and blood pressure skyrocket, sugar pours into the blood, muscles tense for quick action, and the whole metabolism goes into survival mode. This is great if you’re on the African savannah and you hear a lion growling outside your tent. However, Nature never intended this “On your mark! Get set! Go!” response to last more than a moment or two. So when the brain sends a threat message for which there is no swift resolution, the fight-or-flight system stays stuck on “Get set!.” As a result, the immune system is locked into protection mode and is no longer capable of performing the remedial function that is our most powerful defense against cancer.

So when we feel unable to manage or control the changes in our lives caused by prostate cancer, it not only reduces our quality of life, but it is associated with poorer clinical outcomes. In fact, studies in mice, and in tests in human cancer cells grown in the laboratory have found that prolonged psychological stress can enhance a tumor’s ability to grow and spread.

There is always the temptation to alleviate the stress overload of a potentially life-threatening diagnosis with risky behaviors such as drinking alcohol in excess, taking drugs, and over-eating. But this kind of “stress management” only further inhibits immune function. However, maintaining a healthy lifestyle—which means eating well and staying physically active–supports the immune system. As do coping strategies such as prayer. And don’t forget laughter—the ultimate antioxidant.

Here’s how the Discovery Health Web describes the impact of laughter on the immune system: “When we laugh, natural killer cells which destroy tumors and viruses increase, along with Gamma-interferon (a disease-fighting protein), T cells (important for our immune system) and B cells (which make disease-fighting antibodies). As well as lowering blood pressure, laughter increases oxygen in the blood, which also encourages healing.”

The following November 12th, 2015 article comes from the National Cancer Institute (NCI), the largest institute of the National Institutes of Health (NIH). Antioxidants are often advertised to prevent the types of free radical damage that have been associated with cancer development. Multiple large, placebo-controlled, prevention clinical trials have never confirmed this hypothesis. Instead, evidence from two new studies in mice show that antioxidants may actually promote tumor growth and metastasis. For full details see the linked article. As always, this blog is for informational purposes only. If it applies to your health status, please discuss it with your healthcare provider before taking any actions.

A major trial has concluded that a pioneering drug from AstraZeneca, olaparib, developed to treat women with inherited cancers, can also benefit men with certain types of advanced prostate cancer. Olaparib inhibits the enzyme, poly (ADP ribose) polymerase (PARP), a protein used by cancer cells to carry out DNA repairs. PARP inhibitors work on cancers caused by a faulty BRCA1 or BRCA2 gene. Cancerous cells of this type depend on the PARP protein to carry out DNA repairs. If PARP is blocked, cancer cells cannot repair themselves and die.

Olabarib is the world’s first therapeutic agent approved by the FDA in December, 2014 for the treatment of ovarian cancer patients with mutations of the BRCA1 and BRCA2 genes, which play key roles in DNA damage repair. Mutations in these genes have been linked with the development and progression of many tumor types, including prostate cancer. In a recent study published on October 28th, 2015 in the New England Journal of Medicine, researchers found that olaparib is effective in treating the approximately 30% of men with DNA repair defects in their tumors. This illustrates the principle of precision medicine that one can detect prostate cancers with specific targetable mutations using genomic sequencing to deliver more precise cancer care by matching treatment to those men who are most likely to benefit. The trial is also very significant in that it exploits the similarities between prostate, breast and ovarian cancers. In the phase II trial called TOPARP-A, olaparib was found to benefit as many as a third of men (17 out of 49) with metastatic, hormone-resistant prostate cancer, including those who did not inherit cancer genes, but whose tumors acquired defects in DNA repair overtime. Six men had radiological (CT and MRI scan) responses, and eleven had biochemical responses as evidenced by PSA reductions of greater than 50%. Four of the patients had responses that lasted for more than 12 months. Anemia and fatigue were the most common side effects. Olaparib was determined to be effective in stopping prostate cancer growth, generating lasting decreases in prostate specific antigen (PSA) levels, decreases in circulating tumor cell (CTC) counts in the blood, and radiological responses on CT scans and MRI. If approved as a new therapy, men would have to undergo genetic testing looking for defects in DNA repair genes in order to qualify for olaparib. For additional information, see the following linked short article. TOPARP-A, is a major milestone in cancer treatment because it is the first to show the benefit of “precision medicine” in prostate cancer. Precision medicine is a new, transformative model of healthcare that utilizes information from tumor DNA to match a patient with the most effective course of treatment. It is conceivable that drugs such as PARP inhibitors could also increase the effectiveness of common DNA-damaging therapies such as chemotherapy and radiation. For additional information on precision medicine for treatment of certain prostate cancers, see the following linked article published in the OncoTherapy Network.

I recently came across the following menu of prostate cancer diagnostic tests offered by a specific facility. The tests are mainly used to identify those cancers that may be aggressive requiring further biopsies or treatment. The first group of tests would be applicable to men whose PSA values indicate the possibility of cancer while the second group are biopsy-based. This information should be discussed in conjunction with your personal physician and your personal insurance carriers as to need for the tests, their availability, costs and insurance coverage. Information concerning these tests is also available in earlier blogs on this website. To find them, simply insert the test name into the search engine on the home page. In addition, the latest edition of the Prostate Cancer Research Institute (PCRI) Insights (see link) contained an excellent review article discussing all the current prostate MRI techniques.

Post-PSA Diagnostic Testing:4K Score: This test measures four prostate-specific kallikreins in the blood: Total PSA, FREE PSA, Intact PSA and Human Kallikrein 2 (hK2). Results are combined with patient age, digital rectal exam (nodule, no nodule) and prior negative biopsy results (yes, no). The tests then provides a % probability on a scale of 1%-95% for the patient having high-grade prostate cancer. The 4K Score is designed specifically to reduce the number of unnecessary negative biopsies that detect low-grade cancer. This means not all men who have an elevated PSA will require a biopsy.

PCA3 Score: This is a simple urine sample collected following a digital rectal exam for the determination of the PCA3 score. Specific for prostate cancer, and, unlike the PSA, this test is not affected by prostate enlargement or other non-cancerous prostate conditions. In combination with PSA and digital rectal exam (DRE) results, the PCA3 score provides useful information to help decide if a biopsy is needed, or can be delayed. It’s much more specific in giving additional information about the aggressiveness of the cancer if the patient has a positive biopsy.

Post-Biopsy Genetic Testing:MRI-Guided Biopsy: An MRI-ultrasound fusion biopsy involves taking an MRI and then fusing the data with real-time ultrasound images for guidance on biopsy procedures. While there are several types of MRI-guided biopsy techniques, one such system, the UroNav Fusion Biopsy System combines electromagnetic tracking and navigation with an onboard computer and a real-time imaging interface in one mobile workstation. The MR/Ultrasound fusion aligns and registers prior diagnostic MR images with real-time ultrasound images. For a more comprehensive MRI review, see the following link.

Oncotype DX: The Oncotype DX Genomic Prostate Score is a biopsy-based genetic test that can be combined with other measures to predict the aggressiveness of prostate cancer. The test applies advanced genomic science to reveal the unique biology of a tumor in order to optimize cancer treatment decisions for each individual patient. The test is a multi-gene RT-PCR expression analysis developed to work in combination with prostate needle biopsies. It measures the expression of 12 cancer-related genes representing four biological pathways and 5 reference genes, which are then combined to calculate the Genomic Prostate Score (GPX). This biopsy-based score has been clinically validated as a predictor of aggressive prostate cancer. Three studies presented at the 110thAnnual Scientific Meeting of the American Urological Association this year showed this test improved risk assessment for patients and reduces cost of prostate cancer care. This test also is helping to examine further the biology and development of prostate cancer in African American men who are at a high risk for the disease.

Prolaris and Genomic Prostate Score: The purpose of this score is to distinguish between aggressive cancers that need treatment and those that are slow growing and may need active surveillance. The Prolaris Score is a measure of how fast a prostate cancer tumor is growing after a biopsy has indicated its presence in the prostate gland. Biopsy tissue samples are used to determine a patient’s personal Prolaris Score. It measures how fast cancer cells in the tumor are dividing. Measuring a 46-gene expression signature, Prolaris also includes cell cycle progression genes selected based upon correlation with prostate tumor cell proliferation.

Confirm MDx: A genetic test rooted in the field of epigenetics, identifies key changes in gene activity for a negative biopsy or results showing high-grade PIN or ASAP. ConfirmMDx was developed to help reduce unnecessary repeat biopsies through its support of the negative predictive value (NPV). Clinical trials showed this test to be the most significant independent predictor for prostate cancer detection on repeat biopsy. A risk score for ConfirmMDx methylation-positive men was developed to increase the positive predictive value (PPV), which helps identify those with aggressive prostate cancer. This test combines these risk scores along with epigenetic profiling and strongly correlates with the detection of aggressive prostate cancer upon repeat biopsy.

Bayer HealthCare is a strong proponent for men speaking up about prostate cancer. They recently sponsored a symposium on the subject in which I participated. If men were more vocal, prostate cancer funding hopefully might increase following the example of women who are such excellent communicators about breast cancer. The linked Bayer HealthCare site provides video and written information about advanced prostate cancer specifically and a movement entitled Men Who Speak Up.

The Prostate Cancer Foundation (PCF) publishes a highly recommended e mail periodical entitled NewsPulse to which one can subscribe. The October issue contained two articles which I will simply summarize and link.

The first article concluded that popular prostate supplements such as those containing saw palmetto do not benefit prostate cancer patients. They do not decrease the risk of spread of localized disease, affect survival or lower the risk of side effects from radiation therapy. The supplements offered no benefits related to prostate cancer outcomes. However, it should be noted that the article did not address the issue of prostate cancer prevention. The subjects in the study were all prostate cancer patients. As an editorial note, I would not include pomegranate extract in this group of supplements as some positive effects on prostate cancer and PSA doubling time have been observed with the extract (see April 4th, 2011 blog post).

The second article cited a study concerning the effects of the relaxed PSA testing guidelines issued in 2011 by the U.S. Preventative Services Task Force. The current study results indicated that such relaxed screening may delay the diagnosis and treatment of aggressive prostate cancers. Men who could have been eligible for treatment and perhaps cured of more advanced prostate disease may be diagnosed too late. Since 2011, PSA screening has decreased by 28%. The 2011 guidelines did have a positive effect in that diagnoses of new, low-risk cancers dropped by 38%. However, researchers also found a drop of 28% in diagnoses of intermediate-risk cancer and a 23% drop in diagnoses of high-risk cancer one year after the guidelines were published. These finding were consistent with what the researchers hoped would not happen. They concluded that “men will develop more advanced prostate cancer before it is diagnosed and be less likely to be cured.”

A total of 413 relapsing prostate cancer patients whose PSA doubling time was less than nine (9) months and whose PSA was over 1.0 were evaluated. Half of the men were treated with Lupron and the other half received Lupron and Taxotere (docetaxel®). The study information is preliminary after only 2.5 years of follow-up but a statistical trend toward an improvement in cure rates was observed in men treated with Taxotere (docetaxel®) and Lupron.

The preceding abstract was presented at the 2015 meeting of the American Society of Clinical Oncology (ASCO) by Dr. Michael J. Morris of the Memorial Sloan Kettering Cancer Center in New York.